barry-genomicepidemiology-2020.pdf (1.32 MB)
Genomic epidemiology of artemisinin resistant malaria
journal contribution
posted on 2016-03-04, 00:00 authored by R Amato, O Miotto, C J Woodrow, J Almagro-Garcia, I Sinha, S Campino, D Mead, E Drury, M Kekre, M Sanders, A Amambua-Ngwa, C Amaratunga, L Amenga-Etego, V Andrianaranjaka, T Apinjoh, E Ashley, S Auburn, G A Awandare, V Baraka, Alyssa BarryAlyssa Barry, M F Boni, S Borrmann, T Bousema, O Branch, P C Bull, K Chotivanich, D J Conway, A Craig, N P Day, A Djimdé, C Dolecek, A M Dondorp, C Drakeley, P Duffy, D F Echeverry, T G Egwang, R M Fairhurst, A Faiz, C I Fanello, T T Hien, A Hodgson, M Imwong, D Ishengoma, P Lim, C Lon, J Marfurt, K Marsh, M Mayxay, P Michon, V Mobegi, O A Mokuolu, J Montgomery, I Mueller, M P Kyaw, P N Newton, F Nosten, R Noviyanti, A Nzila, H Ocholla, A Oduro, M Onyamboko, J B Ouedraogo, A P P Phyo, C Plowe, R N Price, S Pukrittayakamee, M Randrianarivelojosia, P Ringwald, L Ruiz, D Saunders, A Shayo, P Siba, S Takala-Harrison, T N N Thanh, V Thathy, F Verra, J Wendler, N J White, H Ye, V J Cornelius, R Giacomantonio, D Muddyman, C Henrichs, C Malangone, D Jyothi, R D Pearson, J C Rayner, G McVean, K A Rockett, A Miles, P Vauterin, B Jeffery, M Manske, J Stalker, B Macinnis, D P KwiatkowskiThe current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelch13 mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African kelch13 mutations have originated locally, and that kelch13 shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non-synonymous mutations, many of which cause radical amino-acid changes. Thus, kelch13 is not currently undergoing strong selection in Africa, despite a deep reservoir of variations that could potentially allow resistance to emerge rapidly. The practical implications are that public health surveillance for artemisinin resistance should not rely on kelch13 data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions.
History
Journal
eLifeVolume
5Issue
MARCH2016Article number
ARTN e08714Publisher
ELIFE SCIENCES PUBLICATIONS LTDLocation
EnglandPublisher DOI
Link to full text
ISSN
2050-084XeISSN
2050-084XLanguage
EnglishPublication classification
C1 Refereed article in a scholarly journalUsage metrics
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Science & TechnologyLife Sciences & BiomedicineBiologyLife Sciences & Biomedicine - Other TopicsMOLECULAR POPULATION-GENETICSPLASMODIUM-FALCIPARUMSUBSTITUTION MATRICESSOFT SWEEPSADAPTATIONMUTATIONSEVOLUTIONSIGNATURESMECHANISMPARASITESartemisinindrug resistanceevolutionary biologygenomicsinfectious diseasekelch13malariamicrobiologyplasmodium falciparumMalariaGEN Plasmodium falciparum Community Project
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